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5 day old mouse hippocampus (80 µm section) stained for vessels (Isolectin-B4 – magenta), axons (Neurofilament – green) and cell nuclei (DAPI – blue-contrast staining).

Despite their distinct functions, the nervous and vascular systems regulate each other function and share many more similarities and common principles than previously expected. For example, at the tip of a growing vessel there is a specialized endothelial cell called endothelial tip cell, which senses the cues in the environment and leads the sprouting vessel to its final destination.

Similarly, at the leading edge of a growing axon there is a specialized structure termed the growth cone, responsible for sensing and responding to the guidance cues that will guide the axon to its final target. Interestingly, typical axon guidance cues are also known to regulate blood vessel guidance.

Differentiating neurosphere stained for nuclei (DAPI – blue), astrocytes (GFAP – red) and neurons (beta-III-tubulin – green).

Conversely, for example, the key angiogenic factor, vascular endothelial growth factor (VEGF), and its receptors, are expressed in neuronal cells and participate in processes such as neuronal migration and axon guidance. Despite these initial findings, still little is known about the biology of angiogenic factors in neurons, the signaling pathways that they activate and their functional role in neurodevelopment.

Vibratome section (100 µm) of a E11.5 spinal cord of the Olig2Cre;mTmG mouse line. Olig2 progenitor domain is stained in blue and the progeny of this domain appears in green.

In our lab, we are interested in understanding (i) the signaling pathways and cellular mechanisms that angiogenic molecules exert in neuronal cells and (ii) the communication between the vascular and nervous systems during development. For this, we are using a combination of mouse genetics, organotypic cultures, cell biology, biochemistry and molecular biology approaches.

Vibratom section (100 µm) of E12.5 spinal cord stained for blood vessels (Isolectin-B4 – red), lateral motor columns (FOXP1 – white), motor neurons (Islet½ - blue) and neuronal progenitors (Nestin – green).

Determining how the vascular system, influence neuronal wiring will shed new light in the understanding of the molecular control of neuronal development and the possible causes of neurodevelopmental disorders. Research in this field may suggest new strategies to treat those disorders and to promote axon regeneration after injury or disease.

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